Dry eye is a common disease of the ocular surface affecting millions and is characterized by dryness, irritation, blurred vision and tear instability. One of the key pathological factors of dry eye is an increase in tear osmolarity. Tear film tonicity of dry eye patients generally ranges between 320 and 400 mOsm, and increased tonicity of the tear film has also been reported to be correlated with severity of dry eye disease. Tear film hyperosmolarity causes ocular discomfort and inflammation. Hyperosmolar stress stimulates the production of interleukin-1 (IL-1), IL-6, IL-8 and tumor necrosis factor-α (TNF-α), and proteolytic enzymes such as MMP-9 from corneal epithelial cells.
Hypertonicity causes deleterious altered functioning of the cells, and the immediate effect of hypertonicity is decreased cell volume (cell shrinkage) which is counteracted by accumulation of intracellular components, including inorganic ions and macromolecules, resulting in an immediate and efficient regulation of cell volume. However, this accumulation of inorganic ions can disrupt protein stability and lead to cell death by apoptosis. Hypertonicity-induced apoptosis in human corneal epithelial cells occurs via a cytochrome c-mediated apoptotic pathway which is affected by the JNK and ERK/MAPK signalling pathways. MAP kinases regulate gene transcription by activating transcription factors for cytokines including TNF-α. TNF-α in turn mediates apoptosis by activating caspase-8 through the extrinsic apoptotic pathway and through inflammation. Additionally, increased production of TNF-α by human limbal epithelial cells has been correlated with increasing medium osmolarity.
A significant obstacle to contact lens wear for many people is comfort. Putting aside people who have pre-existing eye conditions that reduce the comfort of contact lens wear, the wearing of contact lenses can cause discomfort in otherwise healthy eyes.
Contact lenses in use today fall into two general categories. Hard type lenses are formed from materials prepared by the polymerization of acrylic esters, such as poly(methyl methacrylate) (PMMA). Gel, hydrogel or soft type lenses are made by polymerizing such monomers as 2-hydroxyethyl methacrylate (HEMA) or, in the case of extended wear lenses, made by polymerizing silicon-containing monomers or macromonomers. An example of a soft type contact lens is a silicone hydrogel lens.
Moreover, in people who have a disorder resulting in an excessively curved cornea or protrusion of the cornea, wearing a contact lens can be an important part of treatment. This is not feasible however if it causes significant discomfort. Also, children are more likely to object to contact lens wear if it is uncomfortable, although it may be preferable for at least some children to wear contact lenses rather than glasses or no eye-correction at all.
It has been reported that discontinuations of contact lens wear can be as high as 50%. Studies have found that the main reason of contact lens drop outs is due to symptoms of ocular discomfort during contact lens wear. It is well known that contact lens drop out is one of the main causes for the global contact lens market being unable to grow. Contact lens wear can cause disruption to the tear film leading to dry eyes. This dry eye can increase the tonicity of the tear film leading to discomfort for the contact lens wearer. Soft contact lenses and extended wear lenses typically contain water, usually 24 to 75% or higher. Evaporation of water from within the contact lens causes the contact lens to replenish this water by absorption of water from the tear layer of the eye. If the tear layer is dehydrated the contact lens becomes uncomfortable and vision is compromised.
There exists a need for compositions and methods for ameliorating the discomfort associated with increased tear film tonicity associated with various diseases and conditions, in particular in contact lens wearers.
Reference to any prior art in the specification is not, and should not be taken as, an acknowledgment or any form of suggestion that this prior art forms part of the common general knowledge in Australia or any other jurisdiction or that this prior art could reasonably be expected to be ascertained, understood and regarded as relevant by a person skilled in the art.